Depressed Mood Improvement Through Nicotine Dosing 3

• Status: Not yet recruiting
• Trial end date: 2026-10-31
• Target enrollment: 0
• Participant gender: All

Summary

Deficits in cognitive control are core features of late-life depression (LLD), contributing both to emotion dysregulation and problems with inhibiting irrelevant information, conflict detection, and working memory. Clinically characterized as executive dysfunction, these deficits are associated with poor response to antidepressants and higher levels of disability. Improvement of cognitive control network (CCN) dysfunction may benefit both mood and cognitive performance, however no current pharmacotherapy improves Cognitive Control Network deficits in LLD.

The study examines the hypothesis that nicotine acetylcholine receptor agonists enhance Cognitive Control Network function. This effect may resultantly improve mood and cognitive performance in LLD. Small, open-label studies of transdermal nicotine (TDN) patches have supported potential clinical benefit and provided support that transdermal nicotine administration engages the Cognitive Control Network.

This blinded study will expand past open-label trials supporting potential benefit in LLD. It will examine TDN's effect on depression severity and cognitive control functions measured by neuropsychological testing. The study will evaluate 60 eligible and enrolled participants over a 3-year period.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Vanderbilt University Medical Center
• Collaborator: National Institute of Mental Health (NIMH)
• Treatments: Nicotine

Criteria

Inclusion Criteria:

1. Age ≥ 60 years;

2. diagnosis of major depressive disorder, single or recurrent episode (DSM5);

3. On a stable therapeutic dose of an allowed SSRI or SNRI for at least 6 weeks;

4. severity: at least mild active depression symptoms, defined as MADRS ≥ 15;

5. cognition: MMSE ≥ 24;

6. fluent in English

Exclusion Criteria:

1. Other Axis I psychiatric disorders, except for generalized anxiety disorder (GAD) or social phobia symptoms occurring in a depressive episode;

2. Use of other augmentation medication treatments for depression (e.g., adjunctive bupropion or other augmenting agents) that the participant does not want to stop, although short-acting sedatives are allowed;

3. Any use of tobacco or nicotine in the last year.

4. Living with a smoker or regular exposure to secondhand smoke.

5. History of alcohol use disorder or substance use disorder of moderate or greater severity (endorsing 4 or more of the 12 criteria) in the last 12 months.

6. Acute suicidality.

7. Acute grief (<1 month);

8. Current or past psychosis.

9. Primary central nervous system neurological disorder, including dementia, stroke, epilepsy, etc.;

10. Presence of unstable medical illness requiring urgent treatment or intervention;

11. MRI contraindication.

12. Electroconvulsive therapy or transcranial magnetic stimulation in last 2 months;

13. Current or planned psychotherapy where the potential participant does not want to pause therapy for the duration of the study;

14. Allergy or hypersensitivity to nicotine patches;

15. In the last 4 weeks, regular use of drugs with central cholinergic or anticholinergic properties or moderate / severe CYP2A6 inhibitors /inducers